Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy
Xiaoxue Xu,1 Yuehan Hao,1 Jiao Wu,2 Jing Zhao,1 Shuang Xiong3 1Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, People’s Republi...
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| Format: | Article |
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Dove Medical Press
2021-04-01
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| Series: | Pharmacogenomics and Personalized Medicine |
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| Online Access: | https://www.dovepress.com/assessment-of-weighted-gene-co-expression-network-analysis-to-explore--peer-reviewed-article-PGPM |
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| author | Xu X Hao Y Wu J Zhao J Xiong S |
| author_facet | Xu X Hao Y Wu J Zhao J Xiong S |
| author_sort | Xu X |
| collection | DOAJ |
| description | Xiaoxue Xu,1 Yuehan Hao,1 Jiao Wu,2 Jing Zhao,1 Shuang Xiong3 1Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, People’s Republic of China; 3Liaoning Academy of Analytic Science, Construction Engineering Center of Important Technology Innovation and Research and Development Base in Liaoning Province, Shenyang, People’s Republic of ChinaCorrespondence: Xiaoxue XuDepartment of Neurology, The First Hospital of China Medical University, No. 155, Nanjing Street, Heping District, Shenyang, Liaoning, People’s Republic of ChinaEmail xiaoxue80cn@sina.comPurpose: This study aimed to explore the key molecular pathways involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) and thereby identify hub genes to be potentially used as novel biomarkers using a bioinformatics approach.Methods: Raw GSE109178 data were collected from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted on the top 50% of altered genes. The key modules associated with the clinical features of DMD and BMD were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID website. A protein-protein interaction (PPI) network was constructed using the STRING website. MCODE, together with the Cytohubba plug-ins of Cytoscape, screened out the potential hub genes, which were subsequently verified via receiver operating characteristic (ROC) curves in other datasets.Results: Among the 11 modules obtained, the black module was predominantly associated with pathology and DMD, whereas the light-green module was primarily related to age and BMD. Functional enrichment assessments indicated that the genes in the black module were primarily clustered in “immune response” and “phagosome,” whereas the ones in the light-green module were chiefly enriched in “protein polyubiquitination”. Eleven essential genes were eventually identified, including VCAM1, TYROBP, CD44, ITGB2, CSF1R, LCP2, C3AR1, CCL2, and ITGAM for DMD, along with UBA5 and UBR2 for BMD.Conclusion: Overall, our findings may be useful for investigating the mechanisms underlying DMD and BMD. In addition, the hub genes discovered might serve as novel molecular markers correlated with dystrophinopathies.Keywords: Duchenne muscular dystrophy, Becker muscular dystrophy, WGCNA, biomarker, pathway |
| first_indexed | 2024-12-14T15:35:02Z |
| format | Article |
| id | doaj.art-dbad0f32f33f46f8804e69ef0209077e |
| institution | Directory Open Access Journal |
| issn | 1178-7066 |
| language | English |
| last_indexed | 2024-12-14T15:35:02Z |
| publishDate | 2021-04-01 |
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| series | Pharmacogenomics and Personalized Medicine |
| spelling | doaj.art-dbad0f32f33f46f8804e69ef0209077e2022-12-21T22:55:45ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662021-04-01Volume 1443144463826Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular DystrophyXu XHao YWu JZhao JXiong SXiaoxue Xu,1 Yuehan Hao,1 Jiao Wu,2 Jing Zhao,1 Shuang Xiong3 1Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, People’s Republic of China; 3Liaoning Academy of Analytic Science, Construction Engineering Center of Important Technology Innovation and Research and Development Base in Liaoning Province, Shenyang, People’s Republic of ChinaCorrespondence: Xiaoxue XuDepartment of Neurology, The First Hospital of China Medical University, No. 155, Nanjing Street, Heping District, Shenyang, Liaoning, People’s Republic of ChinaEmail xiaoxue80cn@sina.comPurpose: This study aimed to explore the key molecular pathways involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) and thereby identify hub genes to be potentially used as novel biomarkers using a bioinformatics approach.Methods: Raw GSE109178 data were collected from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted on the top 50% of altered genes. The key modules associated with the clinical features of DMD and BMD were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID website. A protein-protein interaction (PPI) network was constructed using the STRING website. MCODE, together with the Cytohubba plug-ins of Cytoscape, screened out the potential hub genes, which were subsequently verified via receiver operating characteristic (ROC) curves in other datasets.Results: Among the 11 modules obtained, the black module was predominantly associated with pathology and DMD, whereas the light-green module was primarily related to age and BMD. Functional enrichment assessments indicated that the genes in the black module were primarily clustered in “immune response” and “phagosome,” whereas the ones in the light-green module were chiefly enriched in “protein polyubiquitination”. Eleven essential genes were eventually identified, including VCAM1, TYROBP, CD44, ITGB2, CSF1R, LCP2, C3AR1, CCL2, and ITGAM for DMD, along with UBA5 and UBR2 for BMD.Conclusion: Overall, our findings may be useful for investigating the mechanisms underlying DMD and BMD. In addition, the hub genes discovered might serve as novel molecular markers correlated with dystrophinopathies.Keywords: Duchenne muscular dystrophy, Becker muscular dystrophy, WGCNA, biomarker, pathwayhttps://www.dovepress.com/assessment-of-weighted-gene-co-expression-network-analysis-to-explore--peer-reviewed-article-PGPMduchenne muscular dystrophybecker muscular dystrophywgcnabiomarkerpathway |
| spellingShingle | Xu X Hao Y Wu J Zhao J Xiong S Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy Pharmacogenomics and Personalized Medicine duchenne muscular dystrophy becker muscular dystrophy wgcna biomarker pathway |
| title | Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy |
| title_full | Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy |
| title_fullStr | Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy |
| title_full_unstemmed | Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy |
| title_short | Assessment of Weighted Gene Co-Expression Network Analysis to Explore Key Pathways and Novel Biomarkers in Muscular Dystrophy |
| title_sort | assessment of weighted gene co expression network analysis to explore key pathways and novel biomarkers in muscular dystrophy |
| topic | duchenne muscular dystrophy becker muscular dystrophy wgcna biomarker pathway |
| url | https://www.dovepress.com/assessment-of-weighted-gene-co-expression-network-analysis-to-explore--peer-reviewed-article-PGPM |
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